CTL Escape and Viral Fitness in HIV/SIV Infection

Cytotoxic T lymphocyte (CTL) responses exert a suppressive effect on HIV and simian immunodeficiency virus (SIV) replication. Under the CTL pressure, viral CTL escape mutations are frequently selected with viral fitness costs. Viruses with such CTL escape mutations often need additional viral genome mutations for recovery of viral fitness. Persistent HIV/SIV infection sometimes shows replacement of a CTL escape mutation with an alternative escape mutation toward higher viral fitness. Thus, multiple viral genome changes under CTL pressure are observed in the chronic phase of HIV/SIV infection. HIV/SIV transmission to HLA/MHC-mismatched hosts drives further viral genome changes including additional CTL escape mutations and reversions under different CTL pressure. Understanding of viral structure/function and host CTL responses would contribute to prediction of HIV evolution and control of HIV prevalence.